Discovery of the widespread and impressive properties of fluoroimidazoles as biological substrates and analogs has provided the impetus for the synthesis of other substituted imidazoles. Novel methods have been developed for the synthesis of previously unknown or difficulty accessible 2-substituted imidazoles. Thus, all 2-halohistamines and 2-halohistidines are now available as well as analogues containing the amino, formyl, cyano, and nitro groups. Discovery of a method for the direct introduction of the 2-amino group (via addition of the imidazole carbanion to phenyl azide) provide a basis for the synthesis of the long sought after 2,4-difluoroimidazoles. 2-Trifluoromethylimidazoles, obtained by another novel route, are readily converted to 2-carboxy, 2-carbethoxy, and 2-cyanoimidazoles. The decarboxylation of 1-methyl-4, 5-dicarboxyimidazole occurs exclusively at C-4, showing the mechanism to involve an ylid rather than carbanion. pH dependence studies show that the decarboxylation of nitroimidazolecarboxylic acids also involves an imidazolium ion, despite the extremely low basicity of the ring.